The outcome of the FAST-PS initiative is expected to lead to an enhanced understanding of underlying mechanisms and development of innovative pharmacological treatment approaches for psychotic spectrum disorders. Schizophrenia is a chronic, severe, and disabling mental disorder characterized by deficits in thought processes, perceptions, and emotional responsiveness. This initiative seeks to expeditiously test and analyze novel interventions (i.e., compounds) and their molecular and/or clinical targets for treating clinical dimensions of psychopathology (e.g., anhedonia, cognitive function, social engagement) associated with traditional psychotic spectrum disorders. Of particular interest are features of psychotic spectrum disorders as described in the current DSM-IV-TR diagnostic entities, but not typically identified as the primary target of current clinical therapeutics. As described above, there is interest in the study of mechanisms that cut across traditional disorder categories and where relevant mechanisms and clinical targets are assessed directly rather than being inferred through assignment of a particular diagnosis. The outcome of this initiative is expected to lead to enhanced understanding of specific target engagement by such novel interventions, leading to development of innovative treatment approaches for clinical dimensions of psychopathology associated with traditional psychotic spectrum disorders. In this context, novel interventions (i.e., compounds) may refer either to new chemical entities (NCEs) or to compounds that are being considered for re-purposing from other indications. Testing of compounds that have been FDA-approved for other indications (re-purposing) is of interest if recent basic research discoveries suggest that the compound(s) have the potential to affect a biological mechanism contributing to mental disorders and that has previously been untested in clinical studies. Compounds acting on molecular targets that replicate those of currently marketed psychiatric pharmaceuticals are not of interest for this contract. The primary objective of this contract is: To expeditiously perform small-scale Phase I and/or Phase IIa clinical trials (e.g., First In Human (FIH), Proof of Clinical Mechanism (POCM), Proof of Concept (POC)) to demonstrate target engagement, safety, and early signs of efficacy of such promising compounds in healthy subjects and/or a well-characterized cohort of patients with clinical dimensions of psychopathology associated with traditional psychotic spectrum disorders. Depending on pilot data available for compounds selected for testing, each trial may be a single-site or multisite study with a number of subjects adequate to successfully address the primary aims (e.g., pharmacologic dose range, safety in humans, molecular and/or clinical target engagement, potential biomarkers, biological effects, early signs of efficacy) and inform a judgment whether the particular compound warrants further evaluation.